ABSTRACT ? Project 3 Most complex health conditions do not have a single etiology, but rather develop from exposure to multiple exogenous and endogenous factors that interact to influence individual susceptibility. Failure to consider these multiple and complex interactions reduces the ability of health care providers to accurately predict the occurrence of disease and appropriately target preventive therapies. In Project 3, we propose to leverage the combined expertise of the members of this P50 application with the resources of two pillar studies ? our recently initiated 5-year study (R01 NR014800) assessing the maternal prenatal microbiome as predictive of birth outcomes in a large and socioeconomically diverse cohort of pregnant African American (AA) women; and the analytic and bioinformatic resources of Emory University?s NIH-funded Human Exposome Research Center (HERCULES; P30 ES019776) ? in order to characterize the complex interactions of pre- and postnatal environmental toxicant exposures, microbiome composition, and associated metabolic pathways that underlie the development of two serious child health conditions, preterm birth and neurodevelopmental delay. Preterm birth and neurodevelopmental delay carry lifelong consequences for children and their families. Neither the occurrence of preterm birth nor neurodevelopmental delay is equally distributed within the US population. The incidence of preterm birth in Caucasian infants is 1:10, whereas it is 1:6 for AA infants, resulting in more than 30,000 AA infants born preterm each year in the United States. Neurodevelopmental delay is likewise more common in AA children, and racial disparities in neurodevelopmental delay persist or worsen across development, even when accounting for socioeconomic status and rates of preterm birth. Also more common among AA families are exposures to environmental toxicants, maternal prenatal infections and inflammation, and chronic stress ? all independent risk factors for preterm birth and neurodevelopmental delay. Most recently, race-related differences in the vaginal microbiome have been identified as well, with AA women harboring vaginal microbial communities associated with higher risk of infection. Research to uncover the interactions between these factors and to identify the underpinning molecular pathways has barely begun. In Project 3 we will advance the science in this area by characterizing the following for 300 AA mother- infant pairs derived from the Parent Study: (1) the metabolites and metabolic pathways that associate with preterm birth and neurodevelopmental delay, and (2) the metabolites and pathways that correlate with the maternal prenatal microbiome (data from the Parent Study), maternal prenatal and infant postnatal environmental toxicant exposures (data from Project 1), and the infant microbiome and neurodevelopmental delay (data from Project 2). By unraveling these complex relationships, Project 3 will contribute to the ability to predict these adverse outcomes and appropriately target preventive therapies.